Reproductive tract infections (RTIs) are a public health concern in Ethiopia. However, the relationship between menstrual hygiene management (MHM) and water, sanitation, and hygiene (WASH) factors to RTIs have not been well addressed. A community-based cross-sectional study was conducted from January to March 2019 among 602 systematically selected reproductive-age women aged 15–49 years in Dessie City. Data were collected using a questionnaire and a direct observation checklist. RTIs were identified by the presence during one year before data collection of one or more signs of vaginal discharge, itching/irritation or ulcers/lesions around the vulva, pain during urination and sexual intercourse, and lower abdominal pain and lower back pain. Data were analyzed using multivariable logistic regression analysis with 95%CI . The self-reported prevalence of RTIs was 11.0%(95%CI:8.5–13.7%) during one year prior to the survey. The most commonly reported symptoms of RTI were burning micturition (9.1%) and vaginal discharge (6.1%). Three-fourths 443(75.0%) of households used traditional pit latrines and the majority of the study participants 527(89.2%) did not meet the basic access requirement of 20 liters of water per capita per day. The majority 562(95.1%) of the study participants did not have multiple sexual partners during the last year and 97.8% did not practiced sexual intercourse during menstruation. The most common type of blood-absorbent material used was a sanitary pad 497(84.8%) followed by cloth 89(15.2%). Factors significantly associated with RTIs were using unclean latrines , not washing hands with soap before touching the genital area , history of symptoms of RTIs in the past year , having multiple sexual partners in the past year , changing absorbent material only once per day , and washing the genital area only once per day during menstruation . The self-reported prevalence of RTI showed that one women experienced RTI among ten reproductive-age women. Designing a women’s health policy that focuses on ensuring availability of WASH facilities and improving MHM at the community level is key for sustainably preventing RTIs. Reproductive tract infections (RTIs) are infections of the reproductive system and belong to a group of communicable diseases that are transmitted predominantly by sexual contact  but also include endogenous infections and iatropenic infections linked with unsafe abortions and poor delivery practices . A womanRTIs are among the most common causes of illness among women of reproductive age worldwide and especially in developing countries. Nevertheless, public health research, interventions, and services give very little attention to RTIs . The NatRTIs are highly prevalent in Ethiopia. For instance, in a study of 210 patients conducted at St. Paul’s Hospital in Addis Ababa between September 2015 and July 2016, the overall prevalence of bacterial vaginosis was reported at 48.6% .The impact of menstrual hygiene, which is critical for women, has been largely neglected by water, sanitation, and hygiene (WASH) sector researchers. As a result, millions of women and girls continue to be denied WASH, health, education, dignity, and gender equity . In GujaIf RTIs are left untreated or treatment is delayed, complications can result such as pelvic inflammatory disease, infertility, cervical cancer, puerperal sepsis, chronic pelvic pain, ectopic pregnancy, pregnancy loss, preterm delivery, neonatal blindness, premature membrane rupture, and low birth weight . There iA community-based cross-sectional study was conducted in Dessie City from January to March 2019. Dessie is the capital of South Wollo Zone, located about 400 km from Addis Ababa, the capital of Ethiopia. The city is located at an altitude of 2,470 to 2,550 meters. The Dessie City Administrative Health Office estimated the population of Dessie in 2018/2019 was 223,639, of which 104,800 (46.86%) were males and 118,839 (53.14%) were females  in your submission contain [map/satellite] images which may be copyrighted. All PLOS content is published under the Creative Commons Attribution License (CC BY 4.0), which means that the manuscript, images, and Supporting Information files will be freely available online, and any third party is permitted to access, download, copy, distribute, and use these materials in any way, even commercially, with proper attribution. For these reasons, we cannot publish previously copyrighted maps or satellite images created using proprietary data, such as Google software . For more information, see our copyright guidelines: We require you to either (1) present written permission from the copyright holder to publish these figures specifically under the CC BY 4.0 license, or (2) remove the figures from your submission:1.    You may seek permission from the original copyright holder of Figure(s) [1] to publish the content specifically under the CC BY 4.0 license. http://journals.plos.org/plosone/s/file?id=7c09/content-permission-form.pdf) and the following text:We recommend that you contact the original copyright holder with the Content Permission Form (http://creativecommons.org/licenses/by/4.0/). Please be aware that this license allows unrestricted use and distribution, even commercially, by third parties. Please reply and provide explicit written permission to publish XXX under a CC BY license and complete the attached form.”“I request permission for the open-access journal PLOS ONE to publish XXX under the Creative Commons Attribution License (CCAL) CC BY 4.0  remove the figure or ii) supply a replacement figure that complies with the CC BY 4.0 license. Please check copyright information on all replacement figures and update the figure caption with source information. If applicable, please specify in the figure caption text when a figure is similar but not identical to the original image and is therefore for illustrative purposes only.The following resources for replacing copyrighted map figures may be helpful:http://viewer.nationalmap.gov/viewer/USGS National Map Viewer (public domain): http://eol.jsc.nasa.gov/sseop/clickmap/The Gateway to Astronaut Photography of Earth (public domain): https://www.cia.gov/library/publications/the-world-factbook/index.html and https://www.cia.gov/library/publications/cia-maps-publications/index.htmlMaps at the CIA (public domain): http://earthobservatory.nasa.gov/NASA Earth Observatory (public domain): http://landsat.visibleearth.nasa.gov/Landsat: http://eros.usgs.gov/#USGS EROS (Earth Resources Observatory and Science (EROS) Center) (public domain): http://www.naturalearthdata.com/Natural Earth (public domain): Additional Editor Comments (if provided):There are some issues that need to be addressed for a REVISED VERSION:1- In Table 1 in the age section, 20-year-olds were divided into two parts (15 to 20 and 20 to 34 years old). Why?2- What is the meaning of No formal education in Table 1? Do you mean illiterate people or people who have been educated at home?3- What is meant by Above secondary? Does it mean university education? Or people with a PhD degree? Please write a note.4- In Table 2 for Distance of latrine from thehouse Written 15> and 15-30, Is 15 in the first category or the second?[Note: HTML markup is below. Please do not edit.]Reviewers' comments:Reviewer's Responses to QuestionsComments to the Author1. Is the manuscript technically sound, and do the data support the conclusions?The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: YesReviewer #2: Yes**********2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: YesReviewer #2: Yes**********3. Have the authors made all data underlying the findings in their manuscript fully available?PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.The Reviewer #1: YesReviewer #2: Yes**********4. Is the manuscript presented in an intelligible fashion and written in standard English?PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.Reviewer #1: NoReviewer #2: Yes**********5. Review Comments to the AuthorPlease use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. Reviewer #1: This article is valuable and can be published, but there are some issues that need to be addressed:1- In Table 1 in the age section, 20-year-olds were divided into two parts (15 to 20 and 20 to 34 years old). Why?2- What is the meaning of No formal education in Table 1? Do you mean illiterate people or people who have been educated at home?3- What is meant by Above secondary? Does it mean university education? Or people with a PhD degree? Please write a note.4- In Table 2 for Distance of latrine from thehouse Written 15> and 15-30, Is 15 in the first category or the second?Reviewer #2: This manuscript discusses a much needed work on Menstrual Hygiene Management, Water, Sanitation and Hygiene Remains a Public Health Problem for Women’s in Urbans of South Wollo, Amhara Region, Ethiopia with some basic results. The paper is suitable for publication with following corrections:1. Add some of the most important quantitative results to the Abstract.2. In Discussion and conclusion segment, authors can include the limitations of this study and more ideas and suggestions for prevention and control. The discussion section should be detailed with citation of all the recent references. Add more information about the significance and importance of this study.3. A clear distinction of usage of the statistical tests has to be mentioned.4. Authors should carefully review the final resolution of the figures prior to publication for better understanding of results.5. Cite the source of future investigations in this study.6. Rectify grammatical errors to reach up to international standards.7. Ensure that the references and whole manuscript is as per journal format. Make certain that all the tables and figure citations are also in the standard format.8.The authors are suggested to improve the quality of the language usage and correct grammatical errors.**********what does this mean?). If published, this will include your full peer review and any attached files.6. PLOS authors have the option to publish the peer review history of their article  digital diagnostic tool,  28 Jul 2020Response to reviewersWhen submitting your revision, we need you to address these additional requirements.1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found athttps://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf andhttps://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdfResponse: Thank you for this remark. We re-formatted the revised manuscript using the PLoS ONE format guidelines. The whole content of the manuscript, including the abstract, introduction, methods, discussion and reference are formatted using the guidelines (please see the revised version for each section).2. Please include additional information regarding the survey or questionnaire used in the study and ensure that you have provided sufficient details that others could replicate the analyses. For instance, if you developed a questionnaire as part of this study and it is not under a copyright more restrictive than CC-BY, please include a copy, in both the original language and English, as Supporting Information.Response: We provided the questionnaire in English version and original language as supporting information S I and S II, respectively. http://journals.plos.org/plosone/s/licenses-and-copyright.3. We note that [Figure(s) 1] in your submission contain [map/satellite] images which may be copyrighted. All PLOS content is published under the Creative Commons Attribution License (CC BY 4.0), which means that the manuscript, images, and Supporting Information files will be freely available online, and any third party is permitted to access, download, copy, distribute, and use these materials in any way, even commercially, with proper attribution. For these reasons, we cannot publish previously copyrighted maps or satellite images created using proprietary data, such as Google software . For more information, see our copyright guidelines: We require you to either (1) present written permission from the copyright holder to publish these figures specifically under the CC BY 4.0 license, or (2) remove the figures from your submission:Response: The figure was removed in our submission. Reviewer #1This article is valuable and can be published, but there are some issues that need to be addressed:Response: Thank you for the positive comments on our paper. Your concerns are addressed below. 1- In Table 1 in the age section, 20-year-olds were divided into two parts (15 to 20 and 20 to 34 years old). Why?Response: Thank you very much for finding out such errors. The correct grouping is 15 to 19 (See Table 1). 2- What is the meaning of No formal education in Table 1? Do you mean illiterate people or people who have been educated at home?Response: Sorry for the confusion. We mean they are illiterate. Illiterate not attended both formal and informal education (See Table 1). 3- What is meant by above secondary? Does it mean university education? Or people with a PhD degree? Please write a noteResponse: Primary education means Grade 1-8; secondary education Grade 9-12, and above secondary education means that diploma, degree, masters and others. 4- In Table 2 for Distance of latrine from the house Written 15> and 15-30, Is 15 in the first category or the second?Response: 15 is the second category since for the first category we used less than 15. Reviewer #2Reviewer #2: This manuscript discusses a much needed work on Menstrual Hygiene Management, Water, Sanitation and Hygiene Remains a Public Health Problem for Women’s in Urbans of South Wollo, Amhara Region, Ethiopia with some basic results. The paper is suitable for publication with following corrections:Response: Thank you very much for the positive reflection of our paper. Corrections were made as follows. 1. Add some of the most important quantitative results to the Abstract.Response: We added some of the main quantitative results to the Abstract . 5. Cite the source of future investigations in this study.Response: The recommendations for future investigations are the author’s idea and therefore need no source. 6. Rectify grammatical errors to reach up to international standards.Response: We edited the grammatical errors (see the revised version). 7. Ensure that the references and whole manuscript is as per journal format. Make certain that all the tables and figure citations are also in the standard format.Response: We formatted them as per the journal guidelines. 8.The authors are suggested to improve the quality of the language usage and correct grammatical errors.Response: We edited language usage and grammatical errors. 3 Aug 2020Does menstrual hygiene management and water, sanitation, and hygiene predictors for reproductive tract infections among reproductive age Women in urban Areas of Ethiopia?PONE-D-20-19169R1Dear Dr. Adane (PhD),We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at onepress@plos.org.If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact Kind regards,Hans-Uwe Dahms, Ph.D.Academic EditorPLOS ONEAdditional Editor Comments :This MS has now be revised to an extend that it becomes acceptable.Reviewers' comments:    Accept 5 Aug 2020PONE-D-20-19169R1 Does menstrual hygiene management and water, sanitation, and hygiene predictors for reproductive tract infections among reproductive age Women in urban Areas of Ethiopia? Dear Dr. Adane (PhD):I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. onepress@plos.org.If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. 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Visceral leishmaniasis (VL) is a common infectious disease that is endemic in Iran. This study aimed to investigate the spatial autocorrelation of VL in the northwest of Iran. In this cross-sectional study, the data of all patients were collected in 2009–2017 and analyzed by SPSS23 and Moran's and General G Index. The MaxEnt3.3.3 software was used to determine the ecological niche. A big hot spot area was identified in five counties in the northwest of Iran. More than 70% of the cases were reported from these regions, and the incidence rate increased in the northwest of Iran from 2013 to 2017. Seasonal rainfall and average daily temperature were the most important climate variables affecting the incidence of VL in this region (p < 0.05). Therefore, it can be concluded that VL in the northwest of Iran is expanding to new areas along the border with the Republic of Azerbaijan, and the northeastern section of this region is a high-risk area. Leishmania parasites belonging to the Kinetoplastida class and the family Trypanosomatidae Reviewers' comments:Reviewer's Responses to QuestionsComments to the Author1. Is the manuscript technically sound, and do the data support the conclusions?The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: PartlyReviewer #2: No**********2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: I Don't KnowReviewer #2: No**********3. Have the authors made all data underlying the findings in their manuscript fully available?PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.The Reviewer #1: NoReviewer #2: No**********4. Is the manuscript presented in an intelligible fashion and written in standard English?PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.Reviewer #1: YesReviewer #2: No**********5. Review Comments to the AuthorPlease use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. Reviewer #1: Dear AuthorsPlease consider the following comments:1- Please یouble-check the spelling of the words in all manuscript. For example in title please change leishmaniosis to leishmaniasis.2- The article needs to be edited in English by a native.3- Please define in methodology how did you calculated the incidence of VL?4- Please explain more about the method of analysis for Moran's Index and General G analysis. Did you used the points of disease or considered the counties as the analysis units.5- Please cite a relevant reference for MaxEnt model.6- The reference 24 cited in line 104 seems to be irrelevant to the analysis.7- Fig 5 for the result of spatial auto-correlation should be changed with a map resulted from this analysis.8- In all maps please use "Urmia Lake"9- Table 1 was not included in the reviewed file.10- Please discuss more about the role of weather and environmental variables on the habitat suitability for life cycle of VL.Reviewer #2: This study analyzes the spatial patterns of visceral leishmaniasis in three provinces  in northwestern Iran from 2009 to 2017, as well as its relationship with environmental and geographical factors. The manuscript has a relevant theme, but needs an important review/organization in its content and writing.-I suggest a comprehensive review of the English written in the manuscript ;-Please describe clearly and comprehensively the main problem/object addressed in the manuscript;-The introduction does not provide an entirely relevant description of the proposal and significance of the study. The problem is not significantly and concisely stated in the text;-The methods needs to include some additional methodological details in the text , as well as a comprehensive and detailed description of all analyzes presented in the results;-Overall, the results are not clearly presented and the interpretations and conclusions are not supported and justified by the results, but rather general statements. The limitations of this study are not presented in the text ;-The titles of figures and tables are not provided in the manuscript, and the tables were not included in the main file.**********what does this mean?). If published, this will include your full peer review and any attached files.6. PLOS authors have the option to publish the peer review history of their article  digital diagnostic tool,  13 May 2020Dear editor of the Plos One1) Thank you for your reply. I noted that our ethics committee waived the need for informed consent from the patients and the patients provided consent for the records to be used in this research. 2.) Yes, the Supporting Information files named “GIS Data of VL.xlsx” and “VL Data.xls,” along with the data located in our manuscript, constitute the minimal data set required to replicate the conclusions in our study.3.) Yes, “All relevant data are within the manuscript and its Supporting Information files.”My dear editor, Thank you very much for that patiently and carefully to your comments and we will guide you. I hope I have answered your questions correctly. We worked hard on this study and took the time. This study was conducted in a very important area of endemic disease and with this study, high-risk areas are easily identified for VL disease control and prevention programs.Best regards 1) Thank you once again for your attention to our queries. You have stated that "This data not including the patients characters (name or address)." but it is unclear whether while reviewing patients’ hospital and health records any of the authors had accessed to potentially identifiable information or whether the authors have only accessed fully anonymized records. Could you please clarify this? Please also state in your ethics statement whether the ethics committee waived the need for consent from the patients or whether you obtained informed consent from the patients for their medical records to be used in research/this study. We after receiving the ethics code of the ethics committee of Ardabil University of Medical Sciences We used the database of health centers. This data includes patients who have been previously treated. We used demographic characteristics of patients and place of residence to study. The decision of the ethics committee will also be sent to the appendix.2) Thank you for your additional data sharing information. If you would like to provide an Excel file containing your data, please upload your minimal anonymized data set to your PLOS ONE submission as a Supporting Information file.Ok, we're sending two Excel files that include:A. File the number of patients in the study area.B. The incidence of VL files to different locations for GIS software is used.My dear Anita Estes ,PONE-D-19-35837R1Spatial Autocorrelation and Epidemiological Survey of Visceral Leishmaniasis in an endemic area of Azerbaijan Region, Northwest of IranThank you for better comments. 1) Please include your tables as part of your main manuscript and remove the individual files. Please note that supplementary tables (should remain/ be uploaded) as separate "Supporting Information" files. 2) Thank you for removing the funding-related text from the Acknowledgments Section of your manuscript. Please let us know how you would like to update your Funding Statement. Currently, your Funding Statement reads as follows:"Ardabil University of Medical Sciences"3) Please amend your authorship list in your manuscript file to include all authors. (The names of the authors were checked and there was no problem).4) We note that with regard to the copyright of Figures 1, 6, and 7, you wrote: "I dragged figures 1, 6 and 7 with the Arcmap GIS 10.4.1 software and uploaded the original file of GIS." .https://journals.plos.org/plosone/s/data-availability#loc-minimal-data-set-definition). This may include: a.) The values behind the means, standard deviations and other measures reported; b.) The values used to build graphs; c.) The points extracted from images for analysis. .5) Please confirm whether the data uploaded as Supporting Information files constitutes the minimal data set, defined as the data set used to reach the conclusions drawn in the manuscript with related metadata and methods, and any additional data required to replicate the reported study findings in their entirety .6) If there are ethical or legal restrictions to sharing third-party data used in your study, and the data included as Supporting Information files in your submission does not meet the requirements in the minimal data set definition above, please provide the following: a.) A description of the data set and the third-party source; b.) If applicable, verification of permission to use the data set; and c.) All necessary contact information others would need to apply to gain access to the data. Please note that it is not acceptable for an author to be the sole named individual responsible for ensuring data access. You can find more information on PLOS ONE’s policies regarding acceptable restrictions and third-party data via the following link: Thank you Dr.Eslam Moradi-Asl My dear editor and reviewers ,I'm so sorry. We're in control of corona virus that's why it's late.We tried to respond to all comments individually.We answered every question or comment in front of you.The English were Native.All shapes and maps were edited.We created all the maps ourselves with the Arcmap GIS 10.4.1 software.We wish you all health and good time.PONE-D-19-35837Spatial Autocorrelation and Epidemiological Survey of Visceral Leishmaniosis in an endemic area of Azerbaijan Region, Northwest of IranPLOS ONEAdditional Editor Comments (if provided):-Improve titles in Results section to be more descriptive.  - Include legends to figures. - Check figures axes titles. For example, Y axis in figure 4 is labeled ‘Vl’ instead of ‘VL’. Ok , Edited )-. Please ensure you have thoroughly discussed any potential limitations of this study within the Discussion section. Ok, the limitations of the study were discussed at the end.Journal Requirements:When submitting your revision, we need you to address these additional requirements:http://www.plosone.org/attachments/PLOSOne_formatting_sample_main_body.pdf and http://www.plosone.org/attachments/PLOSOne_formatting_sample_title_authors_affiliations.pdf1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at 2. In the ethics statement in the manuscript and in the online submission form, please provide additional information about the patient records used in your retrospective study. Specifically, please ensure that you have discussed whether all data were fully anonymized before you accessed them and/or whether the IRB or ethics committee waived the requirement for informed consent. If patients provided informed written consent to have data from their medical records used in research, please include this information. 3. Please ensure you have thoroughly discussed any potential limitations of this study within the Discussion section. 4. During your revisions, please note that a simple title correction is required to ensure correct spelling. The title should read: "Spatial Autocorrelation and Epidemiological Survey of Visceral Leishmaniasis in an endemic area of Azerbaijan Region, Northwest of Iran". Please ensure this is updated in the manuscript file and the online submission information. 5. Thank you for stating the following in the Acknowledgments Section of your manuscript:"This work was supported by the Ardabil University of Medical Sciences (Project numbers 92218)."We note that you have provided funding information that is not currently declared in your Funding Statement. However, funding information should not appear in the Acknowledgments section or other areas of your manuscript. We will only publish funding information present in the Funding Statement section of the online submission form.Please remove any funding-related text from the manuscript and let us know how you would like to update your Funding Statement. Currently, your Funding Statement reads as follows:"Ardabil University of Medical Sciences " http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions.6. We note that you have indicated that data from this study are available upon request. PLOS only allows data to be available upon request if there are legal or ethical restrictions on sharing data publicly. For information on unacceptable data access restrictions, please see The Excel and GIS format of the data and maps is sent to the attachment. In your revised cover letter, please address the following prompts:a) If there are ethical or legal restrictions on sharing a de-identified data set, please explain them in detail  and who has imposed them . Please also provide contact information for a data access committee, ethics committee, or other institutional body to which data requests may be sent.http://www.bmj.com/content/340/bmj.c181.long for guidelines on how to de-identify and prepare clinical data for publication. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories.b) If there are no restrictions, please upload the minimal anonymized data set necessary to replicate your study findings as either Supporting Information files or to a stable, public repository and provide us with the relevant URLs, DOIs, or accession numbers. Please see We will update your Data Availability statement on your behalf to reflect the information you provide.http://journals.plos.org/plosone/s/licenses-and-copyright.7. We note that Figures #1, 6 and 7 in your submission contain map images which may be copyrighted. All PLOS content is published under the Creative Commons Attribution License (CC BY 4.0), which means that the manuscript, images, and Supporting Information files will be freely available online, and any third party is permitted to access, download, copy, distribute, and use these materials in any way, even commercially, with proper attribution. For these reasons, we cannot publish previously copyrighted maps or satellite images created using proprietary data, such as Google software . For more information, see our copyright guidelines: We require you to either (1) present written permission from the copyright holder to publish these figures specifically under the CC BY 4.0 license, or (2) remove the figures from your submission:1. You may seek permission from the original copyright holder of Figures #1, 6 and 7 to publish the content specifically under the CC BY 4.0 license. *** I dragged figures 1, 6 and 7 with the Arcmap GIS 10.4.1 software and uploaded the original file of GIS.*****http://journals.plos.org/plosone/s/file?id=7c09/content-permission-form.pdf) and the following text:We recommend that you contact the original copyright holder with the Content Permission Form (http://creativecommons.org/licenses/by/4.0/). Please be aware that this license allows unrestricted use and distribution, even commercially, by third parties. Please reply and provide explicit written permission to publish XXX under a CC BY license and complete the attached form.”“I request permission for the open-access journal PLOS ONE to publish XXX under the Creative Commons Attribution License (CCAL) CC BY 4.0  remove the figure or ii) supply a replacement figure that complies with the CC BY 4.0 license. Please check copyright information on all replacement figures and update the figure caption with source information. If applicable, please specify in the figure caption text when a figure is similar but not identical to the original image and is therefore for illustrative purposes only.The following resources for replacing copyrighted map figures may be helpful:http://viewer.nationalmap.gov/viewer/USGS National Map Viewer (public domain): http://eol.jsc.nasa.gov/sseop/clickmap/The Gateway to Astronaut Photography of Earth (public domain): https://www.cia.gov/library/publications/the-world-factbook/index.html and https://www.cia.gov/library/publications/cia-maps-publications/index.htmlMaps at the CIA (public domain): http://earthobservatory.nasa.gov/NASA Earth Observatory (public domain): http://landsat.visibleearth.nasa.gov/Landsat: http://eros.usgs.gov/#USGS EROS (Earth Resources Observatory and Science (EROS) Center) (public domain): http://www.naturalearthdata.com/Natural Earth (public domain): 8. Please include a copy of Table 2 which you refer to in your text on page 6 and Table 1 and 3 which you refer to in your text on page 7.Ok , was done Reviewer #1: Dear AuthorsPlease consider the following comments:1- Please double-check the spelling of the words in all manuscript. For example in title please change leishmaniosis to leishmaniasis. 2- The article needs to be edited in English by a native.( It was native).3- Please define in methodology how did you calculated the incidence of VL?R:  of the disease was evaluated using SPSS version 234- Please explain more about the method of analysis for Moran's Index and General G analysis. Did you used the points of disease or considered the counties as the analysis units.R:  were calculated and used to evaluate the significance of the index (27). Moran’s I is a commonly used indicator of spatial autocorrelation. In this study, global Moran’s I was used as the first measure of spatial autocorrelation. Its values range from−1 to 1. The value “1” means perfect positive spatial autocorrelation , while “−1” suggests perfect negative spatial auto-correlation (a checkerboard pattern), and “0” implies perfect spatial randomness  . The High/Low Clustering  tool measures how concentrated the high or low values are for a given study area. This tool calculates the High/Low General G value (observed & expected) & the associated Z score & p-value for a given input feature class(30).)5- Please cite a relevant reference for MaxEnt model.. Fort Collins, Colorado. 2011.)6- The reference 24 cited in line 104 seems to be irrelevant to the analysis.( Reference edited ) 7- Fig 5 for the result of spatial auto-correlation should be changed with a map resulted from this analysis. .8- In all maps please use "Urmia Lake" , . 9- Table 1 was not included in the reviewed file. ( This is for Editor) 10- Please discuss more about the role of weather and environmental variables on the habitat suitability for life cycle of VL.Reviewer #2: This study analyzes the spatial patterns of visceral leishmaniasis in three provinces  in northwestern Iran from 2009 to 2017, as well as its relationship with environmental and geographical factors. The manuscript has a relevant theme, but needs an important review/organization in its content and writing. -I suggest a comprehensive review of the English written in the manuscript ; Ok , The manuscript was edited native-Please describe clearly and comprehensively the main problem/object addressed in the manuscript; The introduction was edited -The introduction does not provide an entirely relevant description of the proposal and significance of the study. The problem is not significantly and concisely stated in the text;  and determine the high-risk areas of the disease in the provinces and its relation with environmental and geographical factors. Another objective of the study was to determine the environmental suitability for VL in northwestern Iran for prevention and control of diseases.)-The methods needs to include some additional methodological details in the text , as well as a comprehensive and detailed description of all analyzes presented in the results; Ok, was edited  positive serologic tests was more than 1:3200 cases with medical records, diagnosed by physicians and treated in different parts of the province. By referring to health centers in different counties and reviewing patients’ hospital and health records, demographic characteristics, including age, sex, place of residence, month and year of the disease as well as the results of the DAT test were collected. Then, the data collected were compared with the general statistics in the offices of the vice-chancellor for the health of the provinces of East Azerbaijan, West Azerbaijan, and Ardabil, and the results of the comparison were recorded. The collected data were stored in an ArcMap environment based on the patients’ addresses.))-Overall, the results are not clearly presented and the interpretations and conclusions are not supported and justified by the results, but rather general statements. The limitations of this study are not presented in the text ; Once again the whole article was edited according to your comments and it was native.-The titles of figures and tables are not provided in the manuscript, and the tables were not included in the main file.AttachmentResponse to Reviewers.docxSubmitted filename: Click here for additional data file. 24 Jun 2020PONE-D-19-35837R1Spatial Autocorrelation and Epidemiological Survey of Visceral Leishmaniasis in an endemic area of Azerbaijan Region, Northwest of IranPLOS ONEDear Dr. Moradi-Asl,Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.More specifically, please fully incorporate the two remaining comments made by reviewer 1 in the revised version of the manuscript (i.e. R1). Also, address the few editorial comments made in the ´Aditional Editor Comments´ space right after the signature field at the bottom of this message.plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.Please submit your revised manuscript by Aug 08 2020 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at Please include the following items when submitting your revised manuscript:A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). 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For instructions see: We look forward to receiving your revised manuscript.Kind regards,Albert Schriefer, M.D., Ph.D.Academic EditorPLOS ONEAdditional Editor Comments (if provided):Introduction, line 43. I suggest adjusting ´there is a high correlation between the life cycle of the VL disease and the environmental factors involved in it ...´ to  ´there is a high correlation between the occurrence of the VL disease and the environmental factors involved in it ...´.www.worldclime.com) with a resolution of 30 sec (�1 sq.km) and were used 112 along with an elevation variable at the same resolution to evaluate and determine the appropriate 113 ecological niches (Table 1)´.Methods, lines 111-114. Please, refer to table 1 here: ´A total of 19 climate variables were downloaded from the 111 Worldclime website  and mean diurnal range (21.60%)´. As currently written it is confusing.Results, line 176. Please, correct ´(Table 1and 3)´ to (Table 1)´.[Note: HTML markup is below. Please do not edit.]Reviewers' comments:Reviewer's Responses to QuestionsComments to the Author1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.Reviewer #1: (No Response)Reviewer #2: All comments have been addressed**********2. Is the manuscript technically sound, and do the data support the conclusions?The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: PartlyReviewer #2: Partly**********3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: YesReviewer #2: No**********4. Have the authors made all data underlying the findings in their manuscript fully available?PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.The Reviewer #1: YesReviewer #2: No**********5. Is the manuscript presented in an intelligible fashion and written in standard English?PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.Reviewer #1: YesReviewer #2: No**********6. Review Comments to the AuthorPlease use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. Reviewer #1: Dear AuthorsThank you for addressing most of the comments. Still I think two comments are not addressed:1- Did you used the points of VL disease for Moran's analysis or considered the counties as the analysis units?2- Fig 5 for the result of spatial auto-correlation should be replaced with a map resulted from this analysis. You can ask Arcmap to plot the map i this analysis.Good luckReviewer #2: (No Response)**********what does this mean?). If published, this will include your full peer review and any attached files.7. PLOS authors have the option to publish the peer review history of their article  digital diagnostic tool,  1 Jul 2020My dear editor,Thanks for you and Reviewers and good time.Additional Editor Comments (if provided):1. Introduction, line 43. I suggest adjusting ´there is a high correlation between the life cycle of the VL disease and the environmental factors involved in it ...´ to ´there is a high correlation between the occurrence of the VL disease and the environmental factors involved in it ...´. Ok, was done. www.worldclime.com) with a resolution of 30 sec (�1 sq.km) and were used 112 along with an elevation variable at the same resolution to evaluate and determine the appropriate 113 ecological niches (Table 1)´. Ok, was done.2. Methods, lines 111-114. Please, refer to table 1 here: ´A total of 19 climate variables were downloaded from the 111 Worldclime website  and mean diurnal range (21.60%)´. As currently written it is confusing. Ok, was done and edited . In addition, the impact of all variables together on the model were precipitated again. The model showed that two factors; seasonality (35.40%) and mean diurnal range (21.60%) had the greatest impact on the occurrence of the disease)6. Results, line 176. Please, correct ´(Table 1and 3)´ to (Table 1)´. Ok, was done.Reviewer #1: Dear AuthorsThank you for addressing most of the comments. Still I think two comments are not addressed:1- Did you used the points of VL disease for Moran's analysis or considered the counties as the analysis units? We used the points of VL disease for Moran's analysis.2- Fig 5 for the result of spatial auto-correlation should be replaced with a map resulted from this analysis. You can ask Arcmap to plot the map i this analysis. To determine the autocorrelation, the Moran and G index have been used, and the Arcmap software output is in the form of a graph, not a map.Best regards Dr.Eslam Moradi-AslAttachmentResponse to Reviewers.docxSubmitted filename: Click here for additional data file. 8 Jul 2020Spatial Autocorrelation and Epidemiological Survey of Visceral Leishmaniasis in an endemic area of Azerbaijan Region, Northwest of IranPONE-D-19-35837R2Dear Dr. Moradi-Asl,We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.Within one week, you’ll receive an e-mail detailing the required amendments. 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For more information, please contact Kind regards,Albert Schriefer, M.D., Ph.D.Academic EditorPLOS ONEAdditional Editor Comments :Reviewers' comments: 5 Aug 2020PONE-D-19-35837R2 Spatial autocorrelation and epidemiological survey of visceral leishmaniasis in an endemic area of Azerbaijan region, the northwest of Iran Dear Dr. Moradi-Asl:I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. onepress@plos.org.If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact plosone@plos.org. 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Escherichia coli from river-water and river-sediment in pre-, during- and post-mass bathing events in river Kshipra, Central India.Antibiotic resistance is one of the major global health emergencies. One potential source of dissemination of resistant bacteria is mass gatherings, e.g. mass bathing events. We evaluated the physicochemical parameters of water quality and the antibiotic resistance pattern in commensal E. coli to 17 antibiotics were tested.Water and sediment samples were collected from three selected points during eight mass bathing events during 2014–2016. Water quality parameters  were analyzed using standard methods. In river water and sediment samples, antibiotic susceptibility patterns of isolated E.coli with multi drug resistance (MDR) or extended spectrum beta-lactamase (ESBL) production were between 9–44% and 6–24%, respectively in river-water as well as river-sediment. Total coliform count/ml and E. coli count were higher during-and post-bathing in river water than in pre-bathing period. Thus, the percentage of resistance was significantly higher during and post-bathing period (p<.05) than in pre-bathing. Colony forming unit (CFU)/ml in river-sediment was much higher than in river-water. Percentage of resistance was significantly higher in river-water (p<.05) than in river-sediment.pH, turbidity and dissolved oxygen were significantly lower and total dissolved solid, free carbon dioxide were higher during mass bathing, whilst TSS, BOD and COD were lowest in pre-bathing and highest in post-bathing period. E.coli isolated from the Kshipra River showed significant variation during mass bathing events. Guidelines and regulatory standards are needed to control environmental dissemination of resistant bacteria.Antibiotic resistance in  Clean, pure and safe water exists briefly in nature, as it is immediately polluted by prevailing environmental factors and anthropogenic activities. Industrialization and urbanization has polluted rivers mostly via agricultural runoffs and industrial effluents containing many used or unused antibiotics . AntibioEscherichia coli (E. coli), usually a commensal coliform of humans and animals, enters into the river mainly from livestock operations, their waste products and human septate  images which may be copyrighted. All PLOS content is published under the Creative Commons Attribution License (CC BY 4.0), which means that the manuscript, images, and Supporting Information files will be freely available online, and any third party is permitted to access, download, copy, distribute, and use these materials in any way, even commercially, with proper attribution. For these reasons, we cannot publish previously copyrighted maps or satellite images created using proprietary data, such as Google software . For more information, see our copyright guidelines: We require you to either (1) present written permission from the copyright holder to publish these figures specifically under the CC BY 4.0 license, or (2) remove the figures from your submission:1. You may seek permission from the original copyright holder of Figure 1 to publish the content specifically under the CC BY 4.0 license. http://journals.plos.org/plosone/s/file?id=7c09/content-permission-form.pdf) and the following text:We recommend that you contact the original copyright holder with the Content Permission Form (http://creativecommons.org/licenses/by/4.0/). Please be aware that this license allows unrestricted use and distribution, even commercially, by third parties. Please reply and provide explicit written permission to publish XXX under a CC BY license and complete the attached form.”“I request permission for the open-access journal PLOS ONE to publish XXX under the Creative Commons Attribution License (CCAL) CC BY 4.0  remove the figure or ii) supply a replacement figure that complies with the CC BY 4.0 license. Please check copyright information on all replacement figures and update the figure caption with source information. If applicable, please specify in the figure caption text when a figure is similar but not identical to the original image and is therefore for illustrative purposes only.The following resources for replacing copyrighted map figures may be helpful:http://viewer.nationalmap.gov/viewer/USGS National Map Viewer (public domain): http://eol.jsc.nasa.gov/sseop/clickmap/The Gateway to Astronaut Photography of Earth (public domain): https://www.cia.gov/library/publications/the-world-factbook/index.html and https://www.cia.gov/library/publications/cia-maps-publications/index.htmlMaps at the CIA (public domain): http://earthobservatory.nasa.gov/NASA Earth Observatory (public domain): http://landsat.visibleearth.nasa.gov/Landsat: http://eros.usgs.gov/#USGS EROS (Earth Resources Observatory and Science (EROS) Center) (public domain): http://www.naturalearthdata.com/Natural Earth (public domain): Additional Editor Comments:Expert reviewers have pointed out the need to revise the manuscript updating information on antimicrobial susceptibility testing methodology and controls. Do you have data on colistin susceptibility using MIC method in agar or broth dilution? Please respond to reviewer comments point by point.[Note: HTML markup is below. Please do not edit.]Reviewers' comments:Reviewer's Responses to QuestionsComments to the Author1. Is the manuscript technically sound, and do the data support the conclusions?The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Yes**********2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes**********3. Have the authors made all data underlying the findings in their manuscript fully available?PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.The Reviewer #1: Yes**********4. Is the manuscript presented in an intelligible fashion and written in standard English?PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.Reviewer #1: Yes**********5. Review Comments to the AuthorPlease use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. Reviewer #1: 1. CLSI Performance Standards for Antimicrobial Susceptibility Testing are updated every year. Consequently, testing the antimicrobial susceptibility for Colistin requires MIC with agar or broth microdilution, and can no longer be reported using disk diffusion.2. Kindly justify why this study carried out in 2014-16 is submitted for publication in 2019.**********what does this mean?). If published, this will include your full peer review and any attached files.6. PLOS authors have the option to publish the peer review history of their article  digital diagnostic tool,  23 Jan 2020PONE-D-19-25307Mass-bathing events in River Kshipra, Central India- influence on the water quality and the antibiotic susceptibility pattern of commensal E.coliWe are thankful to the Editor and reviewer for the comments and suggestions required for the improvement of the manuscript. Following are the reply to the various queries and concerns.Editors Comments1. When submitting your revision, we need you to address these additional requirements.Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found athttp://www.journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and http://www.journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdfAuthor's Reply: Formatting done as suggested.2. Funding Statement: The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Author's Reply: Added the statement.http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions.3. We note that you have indicated that data from this study are available upon request. PLOS only allows data to be available upon request if there are legal or ethical restrictions on sharing data publicly. For information on unacceptable data access restrictions, please see In your revised cover letter, please address the following prompts:a) If there are ethical or legal restrictions on sharing a de-identified data set, please explain them in detail  and who has imposed them . Please also provide contact information for a data access committee, ethics committee, or other institutional body to which data requests may be sent.http://www.bmj.com/content/340/bmj.c181.long for guidelines on how to de-identify and prepare clinical data for publication. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories.b) If there are no restrictions, please upload the minimal anonymized data set necessary to replicate your study findings as either Supporting Information files or to a stable, public repository and provide us with the relevant URLs, DOIs, or accession numbers. Please see We will update your Data Availability statement on your behalf to reflect the information you provide.Author's Reply: Supporting files are added.4. We note that Figure 1 in your submission contain [map/satellite] images which may be copyrighted. All PLOS content is published under the Creative Commons Attribution License (CC BY 4.0), which means that the manuscript, images, and Supporting Information files will be freely available online, and any third party is permitted to access, download, copy, distribute, and use these materials in any way, even commercially, with proper attribution. For these reasons, we cannot publish previously copyrighted maps or satellite images created using proprietary data, such as Google software . https://gadm.org/) and display only three sites of sampling. The figure 1 legend now shows all details. Author's Reply: We have now replaced the previous figures and upload the map that is freely available in GADM database :The reviewers comments have been addressed satisfactorily.Reviewers' comments: 20 Feb 2020PONE-D-19-25307R1 E.coli Mass bathing events in River Kshipra, Central India- influence on the water quality and the antibiotic susceptibility pattern of commensal Dear Dr. Purohit:I am pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. onepress@plos.org.If your institution or institutions have a press office, please notify them about your upcoming paper at this point, to enable them to help maximize its impact. If they will be preparing press materials for this manuscript, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact plosone@plos.org. For any other questions or concerns, please email Thank you for submitting your work to PLOS ONE.With kind regards,PLOS ONE Editorial Office Staffon behalf ofDr. Iddya Karunasagar Academic EditorPLOS ONE


The Loran-C system is an internationally standardized positioning, navigation, and timing service system. It is the most important backup and supplement for the global navigation satellite system (GNSS). However, the existing Loran-C signal acquisition methods are easily affected by noise and cross-rate interference (CRI). Therefore, this article proposes an envelope delay correlation acquisition method that, when combined with linear digital averaging (LDA) technology, can effectively suppress noise and CRI. The selection of key parameters and the performance of the acquisition method are analyzed through a simulation. When the signal-to-noise ratio (SNR) is −16 dB, the acquisition probability is more than 90% and the acquisition error is less than 1 μs. When the signal-to-interference ratio (SIR) of the CRI is −5 dB, the CRI can also be suppressed and the acquisition error is less than 5 μs. These results show that our acquisition method is accurate. The performance of the method is also verified by actual signals emitted by a Loran-C system. These test results show that our method can reliably detect Loran-C pulse group signals over distances up to 1500 km, even at low SNR. This will enable the modern Loran-C system to be a more reliable backup for the GNSS system. The Loran-C system is an internationally standardized radio positioning, navigation, and timing (PNT) service system. It has the advantages of high transmission power, long propagation distance, and good phase stability ,2,3. It The Loran-C signal acquisition involves finding the first pulse position of the master and secondary stations without manual intervention. This is a key step in signal processing performed by navigation and timing receivers . With thTherefore, this article proposes an envelope delay correlation (EDC) acquisition method, combined with linear digital averaging (LDA) and adaptive threshold techniques, which can effectively reduce the effect of noise and CRI on the signal acquisition process. Furthermore, the correlation peaks can also be repaired by this method, so that the acquisition results have higher accuracy. The method in this article can accurately and simultaneously detect the signals of the master and secondary stations, thus improving the sensitivity and effective range of Loran-C receivers.The Loran-C signal is formally defined by the United States Coast Guard (USCG) as a sequence of pulses of radio frequency (RF) energy at a central frequency of 100 kHz . A singlThe Loran-C navigation chain is composed of one master station and two to five secondary stations. The pulse groups signal of the master and secondary stations are shown in The interval between the Loran-C pulse groups is called the group repetition interval (GRI) . The GRIThe inherent interference in Loran-C signals is mainly from noise and cross-rate interference ,22. TheyNoise is an integral part of any radio system, and it can originate from sources external to the receiving system or from within the receiving system itself. External sources include lightning discharges, precipitation, electronics and power transmission. The main internal noise source is thermal noise generated in the receiver antenna and front end ,23. The Although each Loran-C station has a different GRI, all Loran-C transmitters transmit their signals with the same frequency and format. Therefore, the signal is often interfered with by signals from other stations in the navigation chain. This is called cross-rate interference (CRI) ,24. A scThe first step in the signal detection process is the acquisition of Loran-C signals, which enables the starting position of the master and secondary pulse group signals to be found. In this article, Loran-C pulse group signals are detected using the envelope delay correlation (EDC) method. This acquisition method is shown in Step 1: The received signal passes through a band-pass filter (BPF) to remove interference and noise outside the band. Its bandwidth is 30 kHz. Step 2: The signal envelope is obtained through quadrature demodulation. The signal envelope is delayed by a GRI, and the correlation peak is obtained using the EDC method, which can reduce the influence of CRI.Step 3: The correlation peak is accumulated and averaged according to the GRI period by using linear digital averaging (LDA) technology, which can restore the Loran-C correlation peak and reduce the influence of interference on the delay correlation peak amplitude.Step 4: The detection threshold is calculated according to the statistical characteristics of the noise in the correlation results. Based on the characteristics of the Loran-C pulse group signal, the correlation peak amplitude is compared with the detection threshold. With this, the acquisition of the master and secondary pulse group signal is achieved.L values of 32, 64, 96, 128, 160, 192, and 224 We assume that the digital Loran-C signal, after passing through the band-pass filter, isrding to ,28:(3)SI signals ,30:(5)I defined as (17)SIR=The waveform of the simulated signal a shows tNoise is the most basic source of interference in the received signal, and it is also inevitable. Generally, the receiving system works normally when the SNR is greater than −10 dB . TherefoCRI is caused by overlapping signals from different Loran-C chains. This will become more severe as the number of stations increases. When the interference signal overlaps with the expected signal, the waveform of the expected signal is affected. The receiving system is required to work normally when the intensity of the CRI signal is lower than the intensity of the expected signal . This seWe test the acquisition method with signals actually transmitted by a real Loran-C system. The test scheme is shown in The actual collected signal is the signal emitted by the BPL timing system in China. The coordinates of the BPL timing system are In order to compare the method in this article with the existing method, we use the existing method to process the collected data. The Loran-C system is a remote land-based radio system that can provide high-precision PNT services. However, the traditional Loran-C acquisition method is unable to effectively suppress noise and CRI. Therefore, with the development of modern Loran-C systems, more advanced Loran-C signal processing capacity is required. In this article, we proposed a Loran-C acquisition method based on the EDC method and analyzed the selection of key parameters in the method. In addition, LDA technology was used to restore the correlation peaks and improve the SNR. This article also described the method of calculating the adaptive detection threshold. We demonstrated that our acquisition method can detect the pulse group signals of the master and secondary Loran-C stations at the same time.In addition, a simulation was used to verify the effectiveness of the acquisition method and analyze its anti-noise and anti-interference performance. The simulation results show that this method can quickly acquire the master and secondary station signals. When the SNR > −16 dB, the acquisition probability reaches more than 90% and the acquisition error is less than 1 μs. When the SIR of the CRI is −5 dB, the method can still detect the pulse group signal effectively because of its ability to suppress interference. Finally, we used our acquisition method to process actual received signals. Those results proved that our method can reliably detect Loran-C pulse group signals over distances up to 1500 km, even at low SNR. Thus, the method has high engineering application value and it is optimized for the design of the new Loran-C navigation and timing receivers. This will improve the performance of the modern Loran-C system, making it a more reliable backup for the GNSS system.


Loran-C is the most important backup and supplement system for the global navigation satellite system (GNSS). However, existing Loran-C demodulation methods are easily affected by noise and skywave interference (SWI). Therefore, this article proposes a demodulation method based on Loran-C pulse envelope correlation–phase detection (EC–PD), in which EC has two implementation schemes, namely moving average-cross correlation and matched correlation, to reduce the effects of noise and SWI. The mathematical models of the EC, calculation of the signal-to-noise ratio (SNR) gain, and selection of the EC schemes are given. The simulation results show that compared with an existing method, the proposed method has clear advantages: (1) The demodulation SNR threshold under Gaussian channel is only −2 dB, a reduction of 12.5 dB; (2) The probability of the demodulated SNR threshold, being less than zero under the SWI environment, can reach 0.78, a 26-fold increase. The test results show that the average data availability of the proposed method is 3.3 times higher than that of the existing method. Thus, our demodulation method has higher engineering application value. This will improve the performance of the modern Loran-C system, making it a more reliable backup for the GNSS. The positioning, navigation, and timing (PNT) system is the key infrastructure in any country considering national economy and security. It provides PNT services for military, commercial, and civil users worldwide ,2. One oThe signal-to-noise ratio (SNR) required for Loran-C data demodulation is higher than that for signal acquisition and detection. Therefore, the demodulation performance determines the timing capability of the Loran-C receiver. In recent years, studies on Loran-C signal receiving methods have mainly focused on ways of enhancing the accuracy of TOA measurements, such as by signal acquisition and detection ,17,18, sTherefore, this article proposes an envelope correlation–phase detection (EC–PD) method to demodulate the Loran-C signal at low SNRs. In this method, two EC schemes, namely moving average-cross correlation (MA–CC) and matched correlation (MC), are used to reduce the effects of noise and SWI, thus significantly improving the timing capability and sensitivity of the Loran-C receiver.The Loran-C signal has been formally defined by the United States Coast Guard (USCG) as a sequence of pulses in the radio frequency (RF) energy range with a central frequency of 100 kHz . The defA(n) denote the normalized envelope of the reference pulse, as shown in λ, and the delay of the SWI is represented by τ. Let m-th Loran-C pulse envelopes in the Loran-C pulse group; thus, the mathematical model of the Loran-C pulse envelope can be expressed as:Let nd noise ,20,21. TN is equal to 200. According to [τ ≥ 35 μs. Therefore, the range of τ discussed in this article is 35–200 μs. In addition, to distinguish the data pulse from the reference pulse, the subscript k is used to express the data pulse, where To reduce the complexity of demodulation, and considering that the energy of a Loran-C pulse signal is mainly concentrated near the envelope peak, we take the duration of the Loran-C pulse signal as 200 μs, i.e., In this study, the EC–PD method is used for a low SNR demodulation of the PPM, in which EC has two implementation schemes: MA–CC and MC. Before the demodulation, the receiver needs to complete the acquisition of the Loran-C pulse signal, which is used to determine the starting positions of the reference and data pulses. Moreover, it needs to identify the skywave to obtain the estimated values of N. The stored ESD of the reference and data pulses are represented by column vectors The first step in the demodulation process is to store the envelope sampling data (ESD) of the reference and data pulses; the storage depth is 1)if 2)if 3)if The phase detection can be carried out using an inverse tangent function with return values in the interval Let This section presents the mathematical models of the EC schemes, laying a foundation for the calculation and analysis of the SNR gain.R zeros before and after the stored ESD, and then replacing the middle value of First, we define a In scheme 2, R. In this simulation, we set From Equation (6), we can easily prove that the noise terms in According to Equation (7), and from the above analysis process, we can easily obtain the equation for calculating the SNR gain of scheme 2, as follows:The magnitude of the SNR gain is an important basis for selecting the EC schemes. Evidently, when there is no SWI, There are two strategies, namely strategy A and strategy B, for selecting the EC schemes. In strategy A, the receiver needs to obtain We present a method to determine We verified the effectiveness of the demodulation method from three aspects. In −3, and is recorded as In addition, we take the SNR threshold as one of the quality parameters to compare the demodulation performances of the above three methods. The SNR threshold mentioned in this article refers to the minimum In this section, the Furthermore, based on the above simulation data, we determined the statistical characteristics of the SNR threshold, represented by the probability distribution, as shown in We test the data demodulation method with signals transmitted by a real Loran-C system. The actual received signal is the Loran-C signal (the GRI is 74.30 ms) emitted by the main station (station ID is 09) of Shandong Rongcheng. This station belongs to China’s Changhe 2 navigation system. The test platform is placed in national time service center of China, 1227.1 km away from the station. (1).In RF signal processing, the input Loran-C signal is sampled by analogue-to-digital and filtered by an adaptive notch and finite impulse response band-pass, thus obtaining the digital signal.(2).The complex envelope of the Loran-C pulse is obtained through orthogonal down conversion.(3).The baseband signal processing includes signal acquisition , carrier(4).The EC–PD and EPD–MD methods are alternately selected for signal demodulation every half an hour.(5).The experimental data are composed of message frames, as shown in The following is the description of the test platform:In the next step, we define two variables, namely the maximum data availability The realization and application of the Loran-C system data link technology can make it possible to build a relatively perfect PNT system by combining with the satellite-based PNT system. However, the existing demodulation method used in the Loran-C system cannot effectively suppress noise and SWI. Therefore, with the development of modern Loran-C systems, a more advanced Loran-C signal processing capability is required. In this study, we developed a Loran-C demodulation method at low SNRs based on the EC–PD, where EC includes two schemes: MA–CC and MC. The mathematical models of the MA–CC and MC, calculation of the SNR gain, and selection of the EC schemes based on the skywave identification results were described in detail. The theoretical analysis results showed that the MA–CC is more suitable for scenarios with SWI, whereas the MC is more suitable for scenarios with only noise. Therefore, the combination of the MA–CC and MC could effectively reduce the effects of noise and SWI on the demodulation process.In addition, a simulation was conducted to verify the effectiveness of the demodulation method and analyze its anti-noise and anti-SWI performances. The simulation results showed that compared with the existing method in , the proThe EC technology proposed in this article has a very low implementation complexity compared with some techniques, such as singular value decomposition ,33 and w


The study aimed to examine the changing incidence of geriatric trauma and evaluate the predictive ability of different scoring tools for in-hospital mortality in geriatric trauma patients.Annual reports released by the National Trauma Database (NTDB) in the USA from 2005 to 2015 and the Trauma Register DGU® in Germany from 1994 to 2012 were analyzed to examine the changing incidence of geriatric trauma. Secondary analysis of a single-center cohort study conducted among 311 severely injured geriatric trauma patients in a level I trauma center in Switzerland was completed. According to the in-hospital survival status, patients were divided into the survival and non-survival group. The differences of the ISS (injury severity score), NISS (new injury severity score), TRISS (Trauma and Injury Severity Score), APACHE II , and SPAS II (simplified acute physiology score II) between two groups were evaluated. Then, the areas under the receiver-operating characteristic curve (AUC-ROC) of different scoring tools for the prediction of in-hospital mortality in geriatric trauma patients were calculated.The analysis of the NTDB showed that the increase in the number of geriatric trauma ranged from 18 to 30% between 2005 and 2015. The analysis of the DGU® showed that the mean age of trauma patients rose from 39.11 in 1993 to 51.10 in 2013, and the proportion of patients aged ≥ 60 years rose from 16.5 to 37.5%. The findings from the secondary analysis showed that 164 (52.73%) patients died in the hospital. The ISS, NISS, APACHE II, and SAPS II in the death group were significantly higher than those in the survival group, and the TRISS in the death group was significantly lower than those in the survival group. The AUCs of the ISS, NISS, TRISS, APACHE II, and SAPS II for the prediction of in-hospital mortality in geriatric trauma patients were 0.807, 0.850, 0.828, 0.715, and 0.725, respectively.The total number of geriatric trauma is increasing as the population ages. The accuracy of ISS, NISS and TRISS was higher than the APACHE II and SAPS II for the prediction of in-hospital mortality in geriatric trauma patients. Trauma is the fourth leading cause of death overall for all ages and the leading cause of death among young people aged less than 45 years . Introduhttps://www.facs.org/quality-programs/trauma/tqp/center-programs/ntdb/docpub) and the Trauma Register DGU® in Germany from 1994 to 2012 (http://www.traumaregister-dgu.de/) were searched to examine the changing incidence of geriatric trauma. Through analysis of the NTDB, the proportion of geriatric trauma and corresponding death rates in the USA were calculated. Based on the data in the DGU® obtained by contacting the Prof. Dr. Rolf Lefering , we calculated the mean age of trauma patients and the proportion of trauma patients aged ≥ 60 years and their trends over time. There is a lack of specific trauma database in China. Thus, we searched the annual reports of the National Bureau of Statistics of the People’s Republic of China (http://www.stats.gov.cn/), and the proportion of population aged ≥ 65 was calculated.The annual reports of the National Trauma Database (NTDB) in the USA from 2005 to 2015 . All statistical process was performed using IBM SPSS 20.0 (Zhejiang University) and P < 0.05 was regarded as statistical significance.Secondary analysis of a single-center cohort study conducted among 311 severely injured geriatric trauma patients in a level I trauma center in Switzerland was completed , 17. Thehttp://www.stats.gov.cn/), the proportion of the population who aged 65 or above increased from 7.7% to 10.1% between 2005 and 2014 , NISS , APACHE II , and SAPS II  in the death group were significantly higher than that in the survival group. The median TRISS was significantly lower in the death group than that in the survival group  .The AUCs were calculated to assess the performance of different scoring tools for the prediction of in-hospital mortality in geriatric trauma patients. Table With the increasingly aging of the population, the incidence of geriatric trauma tends to increase. The study aimed to examine the changing incidence of geriatric trauma and evaluate the predictive ability of different scoring tools for the prediction of in-hospital mortality in geriatric trauma patients. Firstly, through analysis of the annual reports of two large trauma databases, we found the mean age of trauma patients and the proportion of geriatric trauma patients are increasing. Then, secondary analysis of a cohort study showed that the ISS, NISS, and TRISS were better than the SAPS II and APACHE II for the prediction of in-hospital mortality in geriatric trauma patients.Increased life expectancy and independent and active lifestyle expose a great number of elderly people to serious accidents , 20. AddAccurate prognostic expectations are important for decision-making in geriatric trauma patients. Several scoring systems have been developed in an attempt to accurately predict outcomes for trauma patients . The ISSThe APACHE II and SAPS II are generally used to measure the severity and predict outcome for critically ill patients. There was no significant difference between the APACHE II versus the TRISS for the prediction of mortality in severe trauma patients –36. The Some limitations of this study should be acknowledged. Firstly, only the annual reports of two large trauma databases were analyzed to describe the age profile of trauma patients, which may limit the generalization of the results. Then, the geriatric specific scoring system, known as the Geriatric Trauma Outcome Score (GTOS), was not evaluated in the present study , 40. HowThe number and proportion of geriatric trauma patients are increasing rapidly. The ISS, NISS, and TRISS have better performance for the prediction of in-hospital mortality in geriatric trauma patients in comparison with the APACHE II and SAPS II.Additional file 1. List of different scoring tool.


Circular RNAs (circRNAs) are endogenous, single-stranded, most frequently non-coding RNA (ncRNA) molecules that play a significant role in gene expression regulation. Circular RNAs can affect microRNA functionality, interact with RNA-binding proteins (RBPs), translate proteins by themselves, and directly or indirectly modulate gene expression during different cellular processes. The affected expression of circRNAs, as well as their targets, can trigger a cascade of events in the genetic regulatory network causing pathological conditions. Recent studies have shown that altered circular RNA expression patterns could be used as biomarkers in psychiatric diseases, including schizophrenia (SZ); moreover, circular RNAs together with other cell molecules could provide new insight into mechanisms of this disorder. In this review, we focus on the role of circular RNAs in the pathogenesis of SZ and analyze their biomarker and therapeutic potential in this disorder.  The rapid development of novel DNA and RNA sequencing technologies has shed light on the mechanisms of multifactorial disorders, including their probability, origin, development, and pathogenesis ,2,3.Schizophrenia (SZ) is a serious psychiatric disorder that is caused by both environmental and molecular factors . This diIn 2020, the number of published studies aimed at the molecular portrait of SZ has exceeded tens of thousands. However, a significant number of genes, molecular mechanisms, and pathways that are involved in SZ origin and pathogenesis still remain unknown or unclear . UnderstGenome-wide association studies (GWASs) have described only approximately 200 genome SNPs’ susceptibility loci for SZ . Recent It has long been considered that non-coding RNAs (ncRNAs), initially found in eukaryotes, are nothing more than non-functional “junk” RNAs accumulated during the long evolutionary process. Nowadays, many studies have shown that a significant part of this genomic “dark matter” could affect RNA silencing and post-transcriptional regulation of gene expression. As a result of recent advances in high throughput sequencing technologies, thousands of transcribed non-coding RNAs have been described in the vast majority of eukaryotic organisms . These mCircular RNAs (circRNAs) are most frequently non-coding, endogenous, single-stranded RNA molecules that play an important role in cell life. CircRNAs are covalently closed RNA molecules and often originate from protein-coding genes. Previously, it was thought that circular RNAs result from non-functional splicing errors that sometimes occur during the post-transcriptional processes in cells . CurrentRecent studies have shown a significant impact of circRNAs on the origin and development of SZ, as well as an important role of circRNAs in other non-coding and protein-coding gene expression regulation . RecentlMolecular genetic data for circRNAs’ activity in SZ remain limited, despite significant progress made in functional and prediction analysis for this type of RNA ,24,25. TOne analysis of dorsolateral prefrontal cortex (DLPFC) of postmortem healthy and schizophrenic human brains showed significant changes in circRNA expression. A comparison of schizophrenic individuals and healthy controls resulted in the identification of 574 differentially expressed circRNAs, and more than two-thirds of them  were downregulated in SZ. Most importantly, the vast majority of these differentially expressed circular RNAs had miRNA targets and were considered to be potential sponges for microRNAs regulating their activity in the brain . HoweverIt has been also shown that neuronal-enriched circHomer1a  apparently played an important role in cognition processes, as its expression was downregulated in SZ postmortem prefrontal cortex (PFC) area of the human brain, while an intronic circCUL4A  was significantly upregulated .PLEKHA2) was significantly upregulated in peripheral blood mononuclear cells transcriptome ..126].The importance of research and development advances in the molecular therapy for SZ cannot be overestimated, since SZ is the most common variant of psychiatric disorders with cognitive and sensory symptoms and a prominent hereditary component. We suppose that future studies should focus on a deep search for prognostic biomarkers based on genomic, transcriptomic, and epigenetic data and focus on the development of molecular tools and delivery systems to target tissues and organs.